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Surangrat Pongpan 1,2 Objective: To validate a simple scoring system to classify dengue viral infection severity to
Jayanton Patumanond 3 patients in different settings.
Apichart Wisitwong 4 Methods: The developed scoring system derived from 777 patients from three tertiary-care
Chamaiporn Tawichasri 5 hospitals was applied to 400 patients in the validation data obtained from another three tertiary-
Sirianong Namwongprom 1,6 care hospitals. Percentage of correct classification, underestimation, and overestimation was
compared. The score discriminative performance in the two datasets was compared by analysis
1
Clinical Epidemiology Program,
Faculty of Medicine, Chiang Mai
of areas under the receiver operating characteristic curves.
University, Chiang Mai, Thailand; Results: Patients in the validation data were different from those in the development data in
2
Department of Occupational some aspects. In the validation data, classifying patients into three severity levels (dengue fever,
Medicine, Phrae Hospital, Phrae,
Thailand; 3Clinical Epidemiology dengue hemorrhagic fever, and dengue shock syndrome) yielded 50.8% correct prediction
Program, Faculty of Medicine, (versus 60.7% in the development data), with clinically acceptable underestimation (18.6%
Thammasat University, Bangkok, versus 25.7%) and overestimation (30.8% versus 13.5%). Despite the difference in predictive
Thailand; 4Department of Social
Medicine, Sawanpracharak Hospital, performances between the validation and the development data, the overall prediction of the
Nakorn Sawan, Thailand; 5Clinical scoring system is considered high.
Epidemiology Society at Chiang Mai,
Conclusion: The developed severity score may be applied to classify patients with dengue
Chiang Mai, Thailand; 6Department of
Radiology, Faculty of Medicine, Chiang viral infection into three severity levels with clinically acceptable under- or overestimation. Its
Mai University, Chiang Mai, Thailand impact when used in routine clinical practice should be a topic for further study.
Keywords: dengue hemorrhagic fever, dengue shock syndrome, validation, clinical
prediction rule
Introduction
Dengue viral infection is one of the most challenging tropical diseases internationally.1
The infection may be complicated with hypotension2 and bleeding abnormality,
leading to high mortality.2,3 The infection also has high economic impact due to high
cost of care.4,5 Prognostication of disease severity may help clinicians decide which
patients should be admitted to hospital, or which patients may safely be treated as
outpatients.6
A clinical decision rule is a clinical tool that quantifies the individual contributions
that various components of the history, physical examination, and basic laboratory
Correspondence: Sirianong results make toward the diagnosis, prognosis, or likely response to treatment in a
Namwongprom patient. Clinical decision rules attempt to formally test, simplify, and increase the
Department of Radiology, Faculty
of Medicine, Chiang Mai University, accuracy of clinicians’ diagnostic and prognostic assessments.7
Chiang Mai 50200, Thailand A prediction rule for severe dengue infection based on clinical signs and simple labo-
Tel +66 53 945 458
Fax +66 53 945 476
ratory results was successful in predicting dengue hemorrhagic fever (DHF) and dengue
Email snamwong@med.cmu.ac.th shock syndrome (DSS).8 Decision tree algorithms,9–12 diagnostic decision algorithms,13
submit your manuscript | www.dovepress.com Risk Management and Healthcare Policy 2014:7 45–49 45
Dovepress © 2014 Pongpan et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0)
http://dx.doi.org/10.2147/RMHP.S57257
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Pongpan et al Dovepress
the pediatric logistic organ dysfunction score,14–18 and the Table 1 Score assignment scheme for classifying dengue severity
disseminated intravascular coagulation scoring system19,20 Clinical characteristic Criteria Assigned score
were also developed. Other studies were also designed to Age, years .6 1
differentiate dengue fever (DF),9,10 types of dengue infection #6 0
Hepatomegaly Yes 8.5
(DF, DHF, or DSS),10,12,13 fatal conditions,12 development of No 0
DHF,11 multiple organ dysfunctions,14–16 DSS mortality,17,18 Systolic blood pressure, mmHg ,90 2
and disseminated intravascular coagulation.19,20 $90 0
White cell count, /μL .5,000 1
Earlier, we developed a scoring system to help screen
#5,000 0
patient severity21 based on clinical parameters and simple Platelets, /μL #50,000 4.5
laboratory tests. The present study was conducted to exter- .50,000 0
nally validate this scoring system to patients in different Notes: Modified from Pongpan S, Wisitwong A, Tawichasri C, Patumanond J.
Prognostic indicators for dengue infection severity. Int J Clin Pediatr. 2013;2(1):12–18.8
settings. Copyright © 2013 Surangrat Pongpan et al.
46 submit your manuscript | www.dovepress.com Risk Management and Healthcare Policy 2014:7
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Dovepress Validation of dengue severity score
Table 3 Score-derived dengue severity levels in the development (AuROC). The predictive ability of the scoring system of
and the validation data both datasets was graphically compared by the probability
Score-classified Development Validation P-value or risk curves.
severity levels (n=777) (n=400)
Mean score (± SD)
Range
5.6±4.1
0–18
4.2±2.5
0–18
,0.001
Results
Severity levels, n (%) Patients in the development and the validation data were
DF 451 (58.0) 133 (33.3) ,0.001* similar in the presence of the following symptoms and signs:
DHF 276 (35.5) 261 (65.3)
DSS 50 (6.4) 6 (1.5) vomiting, cough, bleeding, systolic blood pressure, diastolic
Note: *P-value from non-parametric test for trend. blood pressure, hematocrit, aspartate aminotransferase,
Abbreviations: DF, dengue fever; DHF, dengue hemorrhagic fever; DSS, dengue prothrombin time, partial thromboplastin time, but were
shock syndrome; SD, standard deviation.
different in gender, age, hepatomegaly, headache, myalgia,
abdominal pain, rash, pleural effusion, petechiae, pulse
Development data pressure, hemoglobin, white cell count, lymphocytes, neu-
The original data used to develop the score were obtained trophils, platelets, and alanine aminotransferase (Table 2).
from three university-affiliated tertiary-care hospitals in The severity score of patients in the development data was
Nakorn Sawan, Kampaeng Phet, and Uttaradit between 2007 higher than in those in the validation data (5.6±4.1 versus
and 2010 (n=777). 4.2±2.5, P,0.001), and the percentage of DSS was higher
(6.4% versus 1.5%, P,0.001) (Table 3).
Validation data In the validation data, classification of patients into three
The validation data were from similar patients as in the severity levels (DF, DHF, and DSS) yielded the following
development data in another three university-affiliated results.
tertiary-care hospitals in Phrae, Lamphun, and Chiang Mai • Patients scoring less than 2.5 predicted DF correctly in
during the same period (n=400). 21.5% (n=86 from 208), with 1-level underestimation in
11% (n=44) and 2-level underestimation in 0.8% (n=3),
Data analysis a total of 11.8% (n=47).
The development data and the validation data were compared • Scores 2.5–11.5 predicted DHF correctly in 28.0%
by exact probability tests or Student’s t-tests or Wilcoxon’s (n=112 from 157), with an underestimation in 6.8%
rank sum tests. The severity score was assigned to the patients (n=27) and an overestimation in 30.5% (n=122).
based on the scoring system proposed from the earlier • Scores above 11.5 predicted DSS correctly in 1.3% (n=5
study, analyzed by multivariable ordinal logistic regression. from 35), with only 1-level overestimation in 0.3% (n=1)
Assigned item scores were derived by transformation of (Table 4).
the coefficients of parameters (Table 1).21 The proportions A total correct prediction was obtained in 50.8%
if correct prediction, underestimation, and overestimation (versus 60.7% in the development data), with an overall
in the development and the validation data were compared underestimation of 18.6% (versus 25.7%) and an overall
by areas under the receiver operating characteristic curves overestimation in 30.8% (versus 13.5%).
Table 4 Score-classified severity and criterion-classified dengue severity in the validation data
Score-classified Score range Criterion-classified severity levels Risk estimation validity*
severity levels DF DHF DSS Over Correct Under
n=208 n=157 n=35 (%) (%) (%)
Mean ± SD 3.3±1.8 4.4±2.1 6.5±3.5
IQR 2.0–4.8 3.8–4.8 4.8–6.8
DF
n=133 ,2.5 86 44 3 – 21.5 11.8
DHF
n=261 2.5–11.5 122 112 27 30.5 28.0 6.8
DSS
n=6 .11.5 0 1 5 0.3 1.3 –
Total 30.8 50.8 18.6
Note: *Percentage of total patients.
Abbreviations: DF, dengue fever; DHF, dengue hemorrhagic fever; DSS, dengue shock syndrome; IQR, interquartile range; SD, standard deviation.
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Pongpan et al Dovepress
Table 5 Discriminative performance of the dengue severity score in the development data and the validation data
Prediction/discrimination Development (n=777) Validation (n=400) P-value
AuROC (%) 95% CI AuROC (%) 95% CI
DHF and DSS versus DF 74.17 72.94–75.37 70.76 68.83–72.43 0.003
DSS versus DF and DHF 88.77 87.88–89.64 75.91 74.18–77.57 ,0.001
Abbreviations: AuROC, area under receiver operating characteristic curve; CI, confidence interval; DF, dengue fever; DHF, dengue hemorrhagic fever; DSS, dengue shock
syndrome.
The ability of the score to discriminate DF from DHF When applied to clinical practice, patients with a low
and DSS was different between the development and the score who are likely to have DF could be treated as outpa-
validation data (AuROC =74.17% versus 70.76%, P=0.003). tients, while those with a higher score who are likely to have
The ability to discriminate DSS from DF and DHF was also DHF could be admitted, and those with the highest score
different (AuROC =88.77% versus 75.91%, P,0.001), as who are likely to have DSS should be admitted for close
shown in Table 5 and Figure 1. monitoring, such as in an intensive care unit.
An impact of application of the score into routine clinical
Discussion practice should be studied further to confirm its usefulness.
The scoring systems for dengue infection in the past were
reported to be successful when validated.24 A simple decision Conclusion
tree using existing data was also successful as a guideline Despite some difference between patients in the validation
to admit DHF patients into hospitals, reducing unnecessary and in the development data, the scoring system could still
admission of mild DF.25 A probability equation and a decision discriminate dengue infection severity with clinically accept-
tree for DHF derived in 2004 and internally validated in 2007 able over- or underestimation. The proposed scoring system
was also successful in predicting DHF at first presentation, is likely to be generalized and applied to routine practice in
avoiding unnecessary hospital admission.26 similar patients and settings.
The scoring system proposed in the prior study21 was less
accurate when validated to the new patients. This reduced Ethical approvals
accuracy may have occurred due to the fact that patients in The present study was approved by the Ethics Committee
the validation data were more severe or less severe than the for Research in Patients, the Faculty of Medicine, Chiang
development data, such as seen in this study. Mai University, and the research ethical committees of the
However, from a clinical perspective, this scoring system six hospitals.
would be useful in routine practice, as it requires only simple
clinical data which can be obtained routinely and is usually Funding
The study was partially funded by the Faculty of Medicine,
available in all levels of patient care centers.
Chiang Mai University.
Acknowledgments
1
DHF
DSS
Disclosure
0.4
Development data
Validation data
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